1. Field of the Invention
The present invention relates to a method for producing a novel β-lactam antibiotic from a protoplast fusion strain, and more particularly to a method for producing a novel β-lactam antibiotic from a protoplast fusion strain of Penicillium chrysogenum and Cephalosporium acremonium. 
2. Description of the Prior Art
Antibiotics are the most effective drugs for curing bacteria-infectious diseases clinically. They have a wide market for their advantages of strong bactericidal effect, low toxicity and small side effect. Among them, β-lactam antibiotics (mainly penicillin and cephalosporin) are widely used since it has very strong bactericidal effect (by blocking cell division) and very low toxicity. It is estimated that the global sales volume of β-lactam antibiotic is about 21 billion USD in 1999.
Among the β-lactam antibiotics, 210 billion USD is almost contributed from 6-APA (6-amino-penicillinic acid, the intermediate of penicillin, as shown in FIG. 1), 7-ACA (7-amino-cephalosporanic acid, the intermediate of cephalosporin, as shown in FIG. 2), and 7-ADCA (7-amino desacetoxi-cephalosporanic acid, the intermediate of cephalosporin, as shown in FIG. 3). That is, the three aforesaid intermediates predominate above 95% market of β-lactam antibiotics.
However, since the antibiotics have been abused for tens of years, drug-resistant bacteria are rapidly increased. As a result, the current commercially available β-lactam antibiotics, even the first-line antibiotics of their second or third generation, cannot repress the spread of the drug-resistant bacteria, which becomes a serious medical problem. Therefore, it is needed to develop a novel β-lactam antibiotic with small side effect and strong bactericidal effect.
To overcome the problems described above, the present invention provides a method for producing a novel β-lactam antibiotic from a protoplast fusion strain of Penicillium chrysogenum and Cephalosporium acremonium. That is, the protoplasts of Penicillium chrysogenum and Cephalosporium acremonium are fused by protoplast fusion to generate a protoplast fusion strain, and a novel β-lactam antibiotic is isolated from this fusion strain. In 1983, Dr. Elander of Brisal Mylc company (Bristal Mylc Squill company now) in USA had tried this method, but he only got the fusion stain, and did not isolate a novel β-lactam antibiotic from the fusion strain (Chang, L. T., Terasaka, D. T. & Elander, R. P. (1982), “Protoplast fusion in industrial fungi”, Developments in Industrial Microbiology 23, 21-29; Elander, R. Pin “Overproduction of Microbial Products” (Krumphonal, R., Sikyta, B., and Vanok, Z.), pp353-369, Academic Press, New York (1982)). However, through profound studies for many years, the present inventors obtain the fusion strain of Penicillium chrysogenum and Cephalosporium acremonium, and isolate the novel β-lactam antibiotic therefrom.